Measuring the concentration of colored substances, called chromophores, inside the human body is of central importance in the medical management of patients, whether in the hospital or at home. Various spectrophotometric devices and methods exist in the art to measure such substances, but all have limitations that make them difficult to use when attempting to measure the bloodstream concentration of a chromophore in vivo.
The majority of spectrophotometric methods are based upon changes in the absorbance of light that occur when the amount of a chromophore encountered by light between emission and detection varies. Outside of the body, changes in the concentration of blood chromophores can be easily estimated using Beer's Law, solved for concentration as: EQU C=A/.epsilon.L, (1)
where C is the concentration, A is the absorbance of light, .epsilon. is a known chemical constant called the extinction coefficient, and L is the distance the light must travel through the blood. Loretz (U.S. Pat. No. 4,357,105) explicitly solves Beer's Law to teach the use of a portable device measuring the hemoglobin concentration in a blood sample placed upon slide, while Lundsgaard (U.S. Pat. No. 4,997,769) and Boucher et al. (U.S. Pat. No. 4,810,090) teach devices and methods for measuring multiple blood components based upon Beer's Law, but only when the blood is removed from the body, and is either flowing through on optical chamber or placed upon a slide.
One likely reason that many have resorted to measurement of blood outside of the body is that Beer's Law fails to work well when applied to blood in vivo. In the body, there are multiple substances that both scatter and absorb light, including bones, hair, and skin pigments, among others. Using multiple wavelengths, it is possible account for some of the absorbance, due to the skin, hair, and other substances, such as is taught by Dahne and Gross (U.S. Pat. No. 4,655,225), but accuracy is often poor. More importantly, simply measuring the total absorbance of light by a body part does not account for the fact that the concentration of many body components is different in the blood than inside tissue cells or in body structures such as bones. Glucose, for example, is often present in higher concentrations in the bloodstream than in tissue cells. This problem is completely ignored by Dahne and Gross, and also by Schlager (U.S. Pat. No. 4,882,492) who teaches a method that allows the measurement of body glucose concentration. thus, the first two essential features of a medically useful spectrophotometer not found in the current art are: 1) that it measure accurately through human tissue in vivo, and 2) that it measure the concentration in the blood, and not simply the total concentration in the body.
One method used to study blood in the body is taught by New, Jr. (U.S. Pat. No. 4,653,498) and others. It was first discovered in Japan in the early 1970's that when light is shined through a finger, there is a slowly-varying (DC) component due to absorbance by the skin, bone, finger, and blood in the veins, as well as a rapidly varying, pulsatile (AC) component that represents the swelling of the tissues with arterial blood during each heartbeat. Subtraction of the DC component from the total absorbance leaves the pulsatile AC signal wave due solely to changes in the volume of arterial blood in the tissue between light emitter and detector. Unfortunately, using this approach, Beer's Law cannot be solved quantitatively as the path length traveled by the light is unknown, and therefore L in Beer's Law remains unknown.
In order to overcome this limitation of an unknown path length, New, Jr. (U.S. Pat. No. 4,653,498), Lehman (U.S. Pat. No. 4,948,248), and others have taught a method of measuring the two types of hemoglobin (the red hemoglobin with oxygen and the blue hemoglobin without oxygen), and taking a ratio of the two absorbances. In this approach, even though L is unknown, L cancels out in the ratio to yield a unitless percentage of hemoglobin in the arteries that is carrying oxygen. This approach has even been modified by Shiga and Suzaki (U.S. Pat. No. 4,927,264) to measure the percentage of hemoglobin in the veins that is carrying oxygen. Unfortunately, when measuring glucose or bilirubin, there are no ratio of two forms of each molecule that are to be measured. Rather, what is important is the concentration of the substance in the bloodstream, a measurement that pulse oximetry inherently cannot make. There are no current devices in the art that can measure an actual blood concentration (as opposed to tissue concentration or unitless percentage ratios of concentration) of glucose, bilirubin, carbon dioxide, or other important components in vivo. Thus, a third essential feature of a medically useful spectrophotometer is: 3) that it measure a concentration (or a concentration based result such as pH, which is a logarithm of concentration in mmol/L), and not simply a unitless percentage or ratio.
Currently, many infants born in this country undergo painful, potentially harmful, blood testing because there is no optical method to effectively determine the concentration in their blood of bilirubin, the pigment responsible for jaundice. As another example, both infants and adults undergo daily, or many times a day, blood testing for blood sugar levels, and could benefit from an optical test method. Other components that could be optically tested include, but are not limited to, hemoglobin, bilirubin, glucose, ketones, cholesterol, water, medications, toxins, products of human metabolism, pH sensitive dyes, and pH sensitive blood components. What is needed, and not available in the current art, is a device that qualitatively measures almost any colored blood component, and that can make quantitative measurements upon which medical decisions can be based.